This proposal requests support for a Keystone Symposia meeting entitled Malnutrition, Gut-Microbial Interactions and Mucosal Immunity to Vaccines, organized by Cecil Czerkinsky, Yasmine Belkaid and John Clemens. Venue details are still being finalized; this meeting will be held in India in November or December of 2011. Malnutrition is among the most devastating health conditions worldwide, affecting one of three children in developing countries and contributing more than ten million deaths annually. The relationship between nutrition and immunity has been a topic of study for more than five decades. Seminal developments in our understanding of the organization and regulation of the immune system have indicated a close relationship between host nutritional status and systemic immunity. However, surprisingly little is known regarding the impact of nutrition on the mucosal immune system of the digestive tract, a system that functions almost independently from the systemic immune apparatus. Recent research also suggests that the composition and metabolic activity of the gut microbiota modulates intestinal barrier function and immune responsiveness (and vice-versa), and can be affected by specific nutrients or lack of these. This meeting will focus on understanding the role of nutrition in modulating gut immunity to vaccines in order to formulate strategies for improving the performance of enteric vaccines in malnourished children. The objective of this symposium is to formulate innovative hypotheses regarding specific mechanisms by which nutrients and defined microbiota affect gut immunity. A better understanding of the links between nutrients, the gut microbiome and the intestinal immune system is likely to pave the way to the development of innovative approaches that target activation of specific immunological pathways for promoting host's gut defense. Such knowledge should impact on the development of vaccine formulations and intervention strategies for improved control of enteric infections in developing countries. The Keystone Symposia meeting on Malnutrition, Gut-Microbial Interactions and Mucosal Immunity to Vaccines will benefit from a partnership with the Bill and Melinda Gates Foundation (BMGF), whereby the 2011 business meeting of the BMGF Grand Challenges in Global Health awardees will be held in conjunction with the Keystone Symposia meeting. PUBLIC HEALTH RELEVANCE: Undernutrition is among the most devastating health conditions worldwide, affecting one in three children in developing countries and linked to more than ten million deaths annually. The relationship between nutrition and immunityhas been a topic of study for more than five decades; however, surprisingly little is known regarding the impact of nutrition on the mucosal immune system of the digestive tract, a system that functions almost independently from the systemic immune apparatus and that is likely to play a key role in responses to many vaccines. The goal of the Keystone Symposia meeting on Malnutrition, Gut-Microbial Interactions and Mucosal Immunity to Vaccines is to formulate innovative hypotheses regarding specific mechanisms by which nutrients and the microorganisms that live in the gut affect gut immunity.